2-hydroxy-3 - (4-hydroxy-3-sulfonamidophenyl) - propylamines useful as beta 3 adrenergic agonists

ABSTRACT

Compounds are provided having the formula  
                 
 
     including pharmaceutically acceptable salts thereof, wherein  
     R 1  is lower alkyl, aryl or arylalkyl;  
     A is hydrogen or  
                 
 
     B is hydrogen, alkyl, alkenyl, or  
                 
 
     but when A is hydrogen, B may only be  
                 
 
     R 2 , R 2′ , R 2″ , R 3  R 3′  and R 3″  are as defined herein;  
     m is 0−3.  
     These compounds possess activity at the beta 3 adrenergic receptor in mammals and are useful in the treatment of diabetes, obesity, depression, achalasia and intestinal hypermotility disorders.

BRIEF DESCRIPTION OF THE INVENTION

[0001] The present invention is directed to compounds of the formula I

[0002] and pharmaceutically acceptable salts thereof. As used in formulaI, and throughout the specification, the symbols have the followingmeanings:

[0003] R¹ is lower alkyl, aryl or arylalkyl;

[0004] A is hydrogen or

[0005] B is hydrogen, alkyl, alkenyl, or

[0006] but when A is hydrogen, B may only be

[0007] R², R^(2′), R^(2″), R³, R^(3′) and R³″ are independentlyhydrogen, hydroxy, alkoxy, difluoromethoxy, trifluoromethoxy,2,2,2-trifluoroethoxy, aryloxy, arylalkoxy, hydroxyalkoxy, lower alkyl,trifluoromethyl, halogen, cyano, alkylthio, alkylsulfinyl,alkylsulfonyl, -(CH₂)_(n)NR⁴COR⁵, -CONR⁴R^(4′), -CO₂R⁵, -NR⁴SO₂R¹,-NR⁴R^(4′), -OCH₂CH₂NR⁴R^(4′), -OCH₂CONR⁴R^(4′), -OCH₂CO₂R⁴,-PO₃R⁴R^(4′) or aryl; or R² and R^(2′) or R³ and R^(3′) may togetherform a carbocycle or heterocycle;

[0008] m is 0−3;

[0009] n=0−3;

[0010] R⁴ and R^(4′) are independently hydrogen or lower alkyl; and

[0011] R⁵ is lower alkyl.

[0012] The compounds of formula I possess activity at the beta 3adrenergic receptor in mammals and are useful in the treatment ofdiabetes, obesity, depression, achalasia and intestinal hypermotilitydisorders.

DESCRIPTION OF THE INVENTION

[0013] The present invention provides for compounds of formula I,pharmaceutical compositions employing such compounds and for methods ofusing such compounds. Listed below are definitions of various terms usedto describe the compounds of the instant invention. These definitionsapply to the terms as they are used throughout the specification (unlessthey are otherwise limited in specific instances) either individually oras part of a larger group.

[0014] The term “alkyl” refers to both straight and branched chaingroups having 1 to 12 carbon atoms, such as methyl, ethyl, propyl,isopropyl, butyl, t-butyl, isobutyl, pentyl, hexyl, isohexyl, heptyl,4,4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, nonyl, decyl, undecyl,and dodecyl. The term “alkyl” also includes cycloalkyl groups having 1to 12 carbon atoms, such as cyclopentyl and cyclohexyl.

[0015] The term “lower alkyl” as employed herein includes such alkylgroups as described above containing 1 to 6 carbon atoms.

[0016] The term “alkoxy” refers to any of the above alkyl groups linkedto an oxygen atom.

[0017] The term “lower alkoxy” refers to any of the above lower alkylgroups linked to an oxygen atom.

[0018] The term “alkenyl” refers to monounsaturated straight andbranched chain groups having 1 to 12 carbon atoms, such as ethenyl,allyl, 3-butenyl, or 2-methylallyl where the point of attachment may beat a saturated or unsaturated carbon atom.

[0019] The term “aryl” refers to monocyclic or bicyclic aromatic groupscontaining from 6 to 10 carbons in the ring portion, such as phenyl,naphthyl, substituted phenyl or substituted naphthyl wherein thesubstituent on either the phenyl or naphthyl may be 1, 2 or 3 loweralkyl groups, halogens or lower alkoxy groups. Phenyl and substitutedphenyl are preferred.

[0020] The term “halogen” or “halo” refers to chlorine, bromine,fluorine or iodine.

[0021] The term “carbocycle” refers to fully saturated or unsaturatedrings of five or six carbon atoms, such as cyclopentane, cyclohexene orbenzene.

[0022] The term “heterocycle” refers to fully saturated or unsaturatedrings of five to fifteen atoms containing one to five oxygen and/orsulfur atoms and/or one to four nitrogen atoms provided that the totalnumber of hetero atoms in the ring is five or less.

[0023] The compounds of formula I can be converted to salts, inparticular pharmaceutically acceptable salts using art recognizedprocedures. The compounds of formula I have at least one basic center,and they can form acid addition salts. These are formed, for example,with strong inorganic acids, such as mineral acids for example sulfuricacid, phosphoric acid or a hydrohalic acid, or with organic carboxylicacids, such as alkanecarboxylic acids of 1 to 4 carbon atoms which areunsubstituted or substituted, for example, by halogen, for exampleacetic acid, such as saturated or unsaturated dicarboxylic acids, forexample oxalic, malonic, succinic, maleic, fumaric, phthalic orterephthalic acid, such as hydroxycarboxylic acids, for exampleascorbic, glycolic, lactic, malic, tartaric or citric acid, such asamino acids, for example aspartic or glutamic acid, or such as benzoicacid, or with organic sulfonic acids, such as alkane- (of 1 to 4 carbonatoms) or arylsulfonic acids, for example methane- or p-toluenesulfonicacid. Corresponding acid addition salts can also be formed having, ifdesired, an additionally present basic center. The compounds of formulaI having at least one acid group (for example COOH) can form salts withbases. Suitable salts with bases are, for example, metal salts, such asalkali metal or alkaline earth metal salts, for example sodium,potassium or magnesium salts, or salts with ammonia or an organic amine,such as morpholine, thiomorpholine, piperidine, pyrrolidine, a mono-,di- or tri-lower alkylamine, for example ethyl-, tert-butyl-, diethyl-,diisopropyl-, triethyl-, tributyl- or dimethylpropylamine, or a mono-,di- or trihydroxy lower alkylamine, for example mono-, di- ortriethanolamine. Corresponding internal salts may furthermore be formed.Salts which are unsuitable for pharmaceutical uses but which can beemployed, for example, for the isolation or purification of freecompounds I or their pharmaceutically acceptable salts, are alsoincluded.

[0024] All stereoisomers of the compounds of the instant invention arecontemplated, either in admixture or in pure or substantially pure form.

[0025] It should be understood that the present invention includesprodrug forms of the compounds of formula I.

[0026] The compounds of the instant invention may be in the free orhydrate form, and may be obtained by methods exemplified by thefollowing descriptions.

[0027] Compounds of formula I can be prepared by reduction of a compoundof formula II (which is a novel intermediate)

[0028] with a reducing agent such as borane or lithium aluminum hydridein a solvent such as tetrahydrofuran at a temperature of 0° to 65° C.

[0029] Compounds of formula II can be prepared by coupling compounds offormula III

[0030] with compounds of formula IV

[0031] using standard protocols for amide bond formation, such asstirring at a temperature of 0° to 65° C. a 1:1 mixture of compounds offormulae III and IV in a solvent such as N,N-dimethylformamide to whichis added a carbodiimide such as1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and acatalyst such as 1-hydroxy-7-azabenzotriazole or 1-hydroxybenzotriazolehydrate.

[0032] The compounds of formula IV are commercially available or areprepared by the methods described in U.S. patent application Ser. No.08/346,543 filed Dec. 2, 1994, PCT Application WO 95/29159 and EP611003, Wu and Pridgen, J. Org. Chem. 1991, 56, 1340-1344, and PridgenAdvances in Asymmetric Synthesis, Vol. 2, pp. 55-117 (1997).

[0033] Compounds of formula III can be prepared by sulfonylation of thecompound of formula V

[0034] with a sulfonylating agent such as methanesulfonyl chloride in asolvent such as pyridine at a temperature of −30° to 30° C.

[0035] The compound of formula V can be prepared by reduction of thecompound of formula VI

[0036] with hydrogen gas at a pressure of one to six atmospheres in analcohol solvent such as methanol or ethanol containing a catalyst suchas 10% palladium on carbon. The compound of formula V is susceptible toair oxidation, should be protected from atmospheric oxygen, and shouldnot be purified prior to conversion to the compound of formula III.

[0037] The compound of formula VI can be prepared by diazotization ofthe commercially available compound of formula VII

[0038] by treatment at about 0° in a solvent such as water with anitrite such as sodium nitrite and a strong mineral acid such assulfuric acid.

[0039] Compounds of formula I having S hydroxyl stereochemistry areprepared from the compound of formula VII that is 3-nitro-L-tyrosine.

[0040] For compounds of formula I having R hydroxyl stereochemistry thecompound of formula VII required is 3-nitro-D-tyrosine.

[0041] The above method for the preparation of compounds of formula Ifrom compounds of formula II through VII is the preferred method ofpreparation. Other methods of preparation of the compounds of formula Iare depicted in the context of Examples below.

[0042] It is understood that in order to incorporate certainsubstituents, protecting groups or functional group manipulations may beused by those skilled in the art. These techniques are described inProtective Groups In Organic Synthesis by T. W. Greene and in the seriesCompendium Of Organic Synthetic Methods, both published by John Wiley &Sons. For example, in cases where R² is a hydroxyl group, that hydroxylgroup may be protected, for example as a benzyl ether, until the laststep when it may be deprotected, for example by catalytic hydrogenation.In cases where R² is a cyano group, that cyano group may be derived froma methoxycarbonyl group by conversion to an aminocarbonyl group bystandard methods, followed by dehydration with for example BurgessReagent ((methoxycarbonylsulfamoyl)triethylammonium hydroxide, innersalt). In cases where a carboxyl group is present in R², that carboxylgroup may be derived from a methoxycarbonyl group by hydrolysis bystandard methods. These strategies for incorporation of substituentsapply equally to cases where the substituent is, or is included in,R^(2′) , R^(2″) , R³, R^(3′) and R^(3″).

[0043] The preferred compounds I of the invention are those where R¹ isalkyl, m=1, where the hydroxyl stereocenter has the S configuration, andthe amino stereocenter has the R configuration, and where A and B arerespectively

[0044] Most preferred are compounds I of the invention where R¹ is CH₃,R² and R^(2′) are each CH₃O (preferably meta and para), R³, R^(3′) andR^(3″) are each H.

[0045] It has been found that the preferred beta 3 agonist activity(with minimal beta 1 and beta 2 agonist activity) of the compounds ofthe invention is associated with the diasteromer where the hydroxylstereocenter has the S configuration and the amino stereocenter has theR configuration. However, compounds of the invention with otherstereochemistries will have the required beta 3 activity as well.

[0046] The present compounds of formula I have activity at the beta 3adrenergic receptor and are therefore useful, for example, in thetreatment of diabetes, obesity, gastrointestinal diseases (such asinflammatory bowel disease, irritable bowel syndrome, nonspecificdiarrhea, and peptic ulcer), achalasia as well as depression.

[0047] Thus a composition containing one (or a combination) of thecompounds of this invention, may be administered to a species of mammal(e.g., humans) suffering from diabetes, obesity, an intestinalhypermotility disorder or achalasia or depression as treatment therefor.

[0048] A single dose, or two to four divided daily doses, provided on abasis of about 0.1 to 100 mg per kilogram of body weight per day,preferably about l to 15 mg per kilogram of body weight per day isappropriate. The substance is preferably administered orally, butintranasal, transdermal and parenteral routes such as the subcutaneous,intramuscular, intravenous or intraperitoneal routes can also beemployed.

[0049] The compounds of this invention can also be formulated incombination with beta 1/beta 2 adrenergic blockers such as propranololand nadolol or stimulants such as salbutamol.

[0050] The compounds of formula I can be formulated for use incompositions such as tablets, capsules or elixirs for oraladministration, in sterile solutions or suspensions for parenteral orintranasal administration, buccal patches, or in transdermal patches,with transdermal patches being preferred. About 10 to 500 mg of acompound of formula I is compounded with a physiologically acceptablevehicle, carrier, excipient, binder, preservative, stabilizer, flavor,etc., in a unit dosage form as called for by accepted pharmaceuticalpractice. The amount of active substance in these compositions orpreparations is such that a suitable dosage in the range indicated isobtained.

[0051] Based on the literature, it is expected that these compounds maybe useful for other indications such as treatment of stress, regulationof intraocular pressure, treatment of conditions associated withincreased protein breakdown such as during convalescence after surgery,treatment of triglyceridemia, hypercholesterolemia, atherosclerotic andcardiovascular diseases, and increasing high density lipoprotein levels.In addition, it is expected that these compounds may be useful as feedadditives for fattening or improving weight gain or increasing lean bodymass in animals and may therefore be used to decrease birth mortalityand increase post-natal survival rates in animals.

[0052] In addition, based on the literature, compounds of formula I areexpected to be useful for improving healing and preventing stomachulcers (K. Kuratani et. al., J. Pharmacol. Exp. Ther., 270, 559 (1994)).The compounds of formula I are also expected to be useful for regulatingcore temperature.

[0053] The following examples and preparations describe the manner andprocess of making and using the invention and are illustrative ratherthan limiting. It should be understood that there may be otherembodiments which fall within the spirit and scope of the invention asdefined by the claims appended hereto.

[0054] The following Examples represent preferred embodiments of thepresent invention.

EXAMPLES

[0055] The compounds of the invention are best prepared by syntheticmethod 1 (SM1), which is detailed below with both a scheme and anexperimental procedure. Examples were prepared by SM1 as well as by lessefficient synthetic methods (SM2, SM3, SM4A, SM4B, SM5A, SM5B, and SM5C)for which synthetic schemes only are shown.

[0056] Reagents are abbreviated in the synthetic schemes as follows: WSC(also EDC) 1-(3-dimethylaminopropyl)-3-ethyl- carbodiimide hydrochlorideHOAT 1-hydroxy-7-azabenzotriazole HOBT.H₂0 1-hydroxybenzotriazolehydrate DMF N,N-dimethylformamide THF tetrahydrofuran MeCN acetonitrilepyr pyridine DMA N,N-dimethylacetamide SEMCl2-(trimethylsilyl)ethoxymethyl chloride RaNi Raney ® Nickel Resin-Cl 1%crosslinked chloromethylated styrene/ divinylbenzene copolymer(Merrifield resin) p-TsOH para-toluenesulfonic acid LAH lithium aluminumhydride TFA trifluoroacetic acid AcOH acetic acid NMO 4-methylmorpholineN-oxide (DHQD)₂PHAL hydroquinidine 1,4-phthalazinediyl diether(DHQ)₂PHAL hydroquinine 1,4-phthalazinediyl diether MsCl methanesulfonylchloride p-TsCl para-toluenesulfonyl chloride TMSCHN₂(trimethylsilyl)diazomethane

[0057]

Example 1

[0058][S-(R*,S*)]-N-[5-[3-[[1-(3,4-Dimethoxyphenyl)-2-phenyl-ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methane-sulfonamide,trifluoroacetate (1:1), prepared by synthetic method 1 (SM1)

[0059] A. (S)-2-Hydroxy-3-(4-hydroxy-3-nitrophenyl)-propanoic acid

[0060] A two liter four-necked flask equipped with a mechanical stirrerwas charged with 3-nitro-L-tyrosine (40.0 g, 0.177 mol, purchased fromAldrich) and distilled water (285 mL). To the resulting thick mixturewas added 10% aqueous sulfuric acid (320 mL, about 0.352 mol, about 2equiv) and water (330 mL). A clear yellow-orange solution was obtained.The reaction vessel was fitted with a pressure equalizing additionfunnel, internal digital thermometer, and gas outlet. The reactionsystem was flushed briefly (about 10 min) with argon to prevent theformation of nitrogen dioxide (brown gas) during the reaction. Thereaction mixture was cooled in an ice bath. At about 5° a precipitatebegan to form and the mixture became noticeably thicker as the reactionapproached 0°. The mixture was cooled to 0.5° before the addition of thesodium nitrite was begun. To the stirred, cold suspension was added asolution of sodium nitrite (39.0 g, 0.565 moles, 3.20 equiv) indistilled water (250 mL) dropwise over 8 h while maintaining thereaction temperature between 0.2-0.50 (ice bath cooling). After stirringfor an additional 3.5 h at 0.3°, the cold bath was removed and thereaction mixture was allowed to warm to room temperature. After stirringfor an additional 17 h, the reaction mixture was filtered (diatomaceousearth) using a minimum amount of water to complete the transfers. Theresulting clear yellow-orange filtrate was extracted with ethyl acetate(5×250 mL). The organic fractions were combined and washed with brine(3×80 mL). After drying (magnesium sulfate), the solvent was removed atreduced pressure to give 36.65 g of crude product as a yellow solid atHPLC purity 94.2% and 95.33% ee by chiral HPLC.

[0061] HPLC analysis for chemical purity was determined on a YMC PackODS-A-(3 micron, 6.0 mm×150 mm) column using gradient elution (10% to90% B solvent over 30 min where A solvent =0.2% phosphoric acid in waterand B solvent=90% acetonitrile in water) at a flow rate of 1.5 mL/minwith detection at220 nm. HPLC analysis for optical purity was determinedon a Chiralcel OJ-R (4.6 mm×150 mm) column using gradient elution (30%to 70% B solvent over 30 min where A solvent=0.2% phosphoric acid inwater and B solvent =methanol) at a flow rate of 0.70 mL/min withdetection at 260 nm.

[0062] This material was combined with that obtained from a similarexperiment that used 37.47 g of starting material and produced productof HPLC purity 93.3 % and 95.22% ee. The combined material was dissolvedwith heating in ethyl acetate (190 mL) to give a clear orange solution.To this hot solution (55°) was slowly added heptane (220 mL) withcontinued heating to 64°. The resulting solution was allowed to coolslightly and seeded. After standing at room temperature for 6 hours themixture was placed at 4° for 18 hours. The resulting solid was collectedby filtration, washed with cold heptane-ethyl acetate (2:1) and driedunder vacuum to give (S)-2-hydroxy-3-(4-hydroxy-3-nitrophenyl)propanoicacid as a bright yellow solid: 57.52 g (71% yield); mp 111°;[α]_(D)=−14.1° (c=0.71, methanol); HPLC purity 97.8%, 95.92% ee bychiral HPLC.

[0063] Elemental Analysis for C₉H₉NO₆

[0064] Calculated: C, 47.58; H, 3.99; N, 6.17

[0065] Found: C, 47.38; H, 3.73; N, 6.17

[0066]¹³C NMR (100.625 MHz, CD₃CN) δ174.83, 154.40, 140.16, 134.48,130.89, 126.40, 120.34, 71.23, 39.22

[0067]¹H NMR (400.13 MHz, CD₃CN) δ10.10 (1H, br s), 7.88 (1H, d), 7.43(1H, dd), 6.99 (1H, d), 4.26 (1H, dd), 3.70 (1H, br s), 2.98 (1H, dd),2.79 (1H, dd).

[0068] B. (S)-2-Hydroxy-3-(4-hydroxy-3-(methylsulfonyl)-aminophenyl)protanoic acid

[0069] A solution of (S)-2-hydroxy-3-(4-hydroxy-3-nitrophenyl)propanoicacid (9.2 g, 41 mmol) in 150 mL of methanol was hydrogenated, afteraddition of 0.5 g of 10% palladium on carbon, for 24 h at 45 psi using aParr shaker. After filtration through Celite under a blanket of nitrogengas, the volatiles were removed using a rotary evaporator. The flask wasflushed with nitrogen before addition of 30 mL of dry pyridine. Once thestirred suspension formed a homogeneous solution, the flask wascooled-under nitrogen to −20° and methanesulfonyl chloride (5.0 g, 44mmol) was added over 5 min. After stirring for 1 h at −20°, the flaskwas placed in a −12° freezer for 24 h. To quench the reaction, 50 mL ofwater was added and the volatiles were removed using a rotary evaporatorwith a bath temperature of 50°. A second 50 mL portion of water wasadded and removed as previously described. The resultant crude red oilwas chromatographed on Mitsubishi Chemical Industries CHP-20P resin(75-150 micron) using 15-25% methanol/water to elute the product. Afterevaporative removal of methanol, the residual solution was lyophilizedto yield 6.8 g (63%) of(S)-2-hydroxy-3-(4-hydroxy-3-(methylsulfonyl)aminophenyl)propanoic acid.

[0070] C.[S-(R*,S*)]-N-[5-[3-[[1-(3,4-Dimethoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxy-phenyl]methanesulfonamide,trifluoroacetate (1:1)

[0071] To the solution of(S)-2-hydroxy-3-(4-hydroxy-3-(methylsulfonyl)aminophenyl)propanoic acid(910 mg, 3.3 mmol) in 10 mL dry N,N-dimethylformamide was added1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (690 mg, 3.6mmol), 1-hydroxy-7-azabenzotriazole (490 mg, 3.6 mmol), and(R)-1-(3,4-dimethoxyphenyl)-2-phenylethylamine (771 mg, 3.0 mmol) atroom temperature under argon. The reaction mixture was heated at 60° forone hour. HPLC analysis indicated the reaction was complete. Solvent wasremoved under reduced pressure and the residue was co-evaporated withtoluene (3×20 mL). The residue was redissolved in ethyl acetate (200 mL)and this was washed sequentially with 1N aqueous hydrochloric acid (50mL), water (50 mL) and brine (50 mL). The organic phase was dried(sodium sulfate) and concentrated under reduced pressure to yield 1.62 gof yellow oil. This crude amide intermediate could be purified by silicagel chromatography eluting with ethyl acetate/hexane, but was it was notpurified in this case. The crude amide was dissolved in 25 mL of drytetrahydrofuran and borane dimethylsulfide complex (3 mL of 10 Msolution in tetrahydrofuran, 30 mmol) was added at room temperatureunder argon. The mixture was refluxed for one day and HPLC analysisindicated the reaction was complete. Saturated aqueous ammonium chloridesolution (30 mL) was carefully introduced and the resulting mixture wasstirred at 60° for one hour. The layers were separated and the aqueous.layer was extracted with ethyl acetate (2×50 mL). The combined organicphases were washed with water (50 mL), brine (50 mL), the dried (sodiumsulfate). Concentration under reduced pressure yielded 1.23 g of yellowoil. The crude product was purified by preparative HPLC on a YMC ODS A20 mm×100 mm 5 micron column using gradient elution (30% to 100% Bsolvent over 8 min with 4 min hold time at 100% B where A solvent=90%water, 10% methanol, 0.1% trifluoroacetic acid and B solvent=10% water,90% methanol, 0.1% trifluoroacetic acid) with a flow rate of 20 mL/minwith detection at 220 nm. This afforded 989 mg (54%) of title compoundas the trifluoroacetic acid salt. HPLC analysis indicated greater than98% purity. Alternately, the crude product could be purified by silicagel chromatography eluting with 2% methanol/dichloromethane. Thetrifluoroacetic acid salt could then be obtained by addition of 1 equivof trifluoroacetic acid to a methanol solution of the title compoundfree base, followed by solvent evaporation. Characterization of thetitle compound appears in the accompanying table of Examples.

[0072] The accompanying table of Examples indicates the actual syntheticmethod used to prepare each Example and provides characterization ofeach Example compound.

[0073] Regarding the Example compounds’ mass spectral data, mass tocharge ratios confirming (M+H)⁺ are reported. Two lines are listed incases where the two are of similar intensity and represent isotopicforms such as compounds containing one bromine or two chlorine atoms. Ina few cases (M−H)⁻ is reported. These are listed in parentheses.

[0074] Regarding the Example compounds’ HPLC data, analytical HPLCretention times are reported in minutes along with the methods used asdefined below. Shimadzu analytical HPLC systems were used for all HPLCanalyses. In all cases gradient elution of 0% to 100% B solvent was usedover the time period indicated. Solvent A is 10% methanol, 90% water,0.2% phosphoric acid. Solvent B is 90% methanol, 10% water, 0.2%phosphoric acid. HPLC method: LC1 column: YMC S5 ODS 4.6 × 50 mm flowrate: 4.0 mL/min gradient time: 4 min detection: 220 nM HPLC method: LC2column: YMC S3 ODS 4.6 × 50 mm flow rate: 2.5 mL/min gradient time: 8min detection: 254 nM HPLC method: LC3 column: YMC S5 ODS 4.6 × 50 mmflow rate: 3.0 mL/min gradient time: 4 min detection: 220 nM HPLCmethod: LC4 column: YMC S3 ODS 4.6 × 50 mm flow rate: 2.5 mL/mingradient time: 8 min detection: 220 nM HPLC method: LC5 column: YMC S3ODS 6.0 × 150 mm flow rate: 1.5 mL/min gradient time: 30 min detection:220 nM HPLC method: LC6 column: YMC S3 ODS 6.0 × 150 mm flow rate: 1.5mL/min gradient time: 40 min detection: 220 nM HPLC method: LC7 column:Zorbax SB-C18 4.5 × 75 mm flow rate: 2.5 mL/min gradient time: 8 mindetection: 220 nM

[0075] Regarding the Example compounds’ ¹H NMR data, chemical shifts arelisted in ppm downfield of tetramethyl-silane (δ) and coupling constants(J valves) are listed in hertz (Hz). The spectra for Examples 29, 51 and55 vary significantly with concentration in deutero-chloroform. ExampleStructure Name Synthesis MS HPLC 1H NMR Chiral 1

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxylphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM1, SM3 501 5.4 - LC7 (370 MHz, CD3OD) 2.50-2.80(m, 3H), 2.88(s,3H), 2.89(dd, 1H), 3.22(dd, 1H), 3.38(dd, 1H), 3.78(s, 3H), 3.81(s, 3H),4.02 (m, 1H), #4.36(dd, 1H), 6.72-6.93(m, 5H), 6.99(m, 2H), 7.08-7.23(m,4H) Chiral 2

[R-(R*, R*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM3 501 5.4 - LC7 (270 MHz, CD3OD), 2.58(dd, 1H), 2.87(s, 3H),2.67-2.90(m, 3H), 3.17(dd, 1H), 3.44(dd, 1H), 3.75 (s, 3H), 3.80(s, 3H),#3.85(m, 1H), 4.35 (dd, 1H), 6.72-6.90(m, 5H), 6.99(m, 2H), 7.05-7.23(m,4H) Chiral 3

[S-(R*, R*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM3 501 17.6 - LC5 (400 MHz, CD3OD) 2.58 (dd, 1H), 2.72(dd, 1H),2.83 (dd, 1H), 2.87(s, 3H), 3.0 (1H, overlapped with singlet), 3.17(dd,1h), 3.46(dd, 1H), #3.75 (s, 3H), 3.80(s, 3H), 3.84 (dd, 1H), 4.35(dd,1H), 6.7-6.9 (m, 5H), 7.00(d, 2H), 7.10(s, 1h), 7.1-7.2(m, 3H) Chiral 4

[R-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM3 501 17.5 - LC5 (400 MHz, CD3OD) 2.5-2.8 (m, 3H), 2.88(s, 3H),3.0(1H, overlapped with singlet), 3.21 (dd, 1H), 3.4(overlapped withsolvent, 1H), #3.77(s, 3H), 3.80 (s, 3H), 4.0-4.1(m, 1H), 4.3-4.4 (m,1H), 6.7-6.95(m, 5H), 6.95-7.1(m, 2H), 7.10(s, 1H), 7.1-7.3 (m, 3H) 5

(1R)-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM4A 501 18.6 - LC5 6

(2S)-N-[5-[3-[[10(3,4- Dimethoxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM1 501 17.5 - LC5 7

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(2- methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]methanesulfonamide,trifluoroacetate(1:1). SM5A 471 3.5 - LC3 Chiral 8

[S-(R*,S*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1-(3- methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]methanesulfonamide,trifluoroacetate(1:1). SM3 471 5.7 - LC7 (270 MHz, CD3OD), 2.50-2.78 #m,3H), 2.89(s, 3H), 2.91(m, 1H), 3.19(dd, 1H), 3.39(dd, 1H), 3.74(s, 3H),4.01(m, 1H), 4.40 (dd, 1H), 6.75-6.87(m, 4H), 6.89(dd, 1H), 6.99(m, 2H),7.08 7.29(m, 5H) 9 Chiral [R-(R*,R*)]-N-[2-Hydroxy-5-[2-hydroxy-3-[[1-(3- methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]methanesulfonamide,trifluoroacetate(1:1). SM3 471 2.9 - LC1 (270 MHz, CD3OD), 2.59(dd, 1H),2.88(s, 3H), 2.65-2.90 #(m, 3H), 3.17(dd, 1H), 3.45(dd, 1H), 3.73(s,3h), 3.89(m, 1h), 4.39(dd, 1H), 6.l72-6.86(m, 4H), 6.89(dd, 1H),6.94-7.03 (m, 2H), 7.08-72.9(m, 5H) Chiral 10

[S0(R*,S*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1-(4- methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]methanesulfonamide,trifluoroacetate(1:1). SM3 471 5.6 - LC7 (270 MHz, CD3OD) 2.50-2.78(m,3H), 2.86(m, 1H), 2.89(s, #3H), 3.21(dd, 1H), 3.37(dd, 1H), 3.78(s, 3H),4.01(m, 1H), 4.38 (dd, 1H), 6.75-6.95(m, 4h), 6.99(m, 2H), 7.05-7.25(m,6H) Chiral 11

[R-(R*,R*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1-(4- methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]methanesulfonamide,trifluoroacetate(1:1). SM3 471 2.9 - LC1 (270 MHz, CD3OD) 2.59(dd, 1H),2.88(s, 3H), 2.63-2.90(m, 3H), #3.18(dd, 1H), 3.44(dd, 1H), 3.78(s, 3H),3.86(m, 1H), 43.6(dd, 1H), 6.73-6.90(m, 4H), 6.99(m, 2H), 7.07-7.23(m,6H) Chiral 12

[S-(R*,S*)]-N-[5-[3-[]1-[4- (Difluoromethoxy)phenyl]-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM2 507 6.4 - LC7 (270 MHz, CD3OD)2.51-2.79(m, 3H), 2.83(s, 3H), #2.90(m, 1H), 3.21(dd, 1H), 3.42(dd, 1H),4.02(m, 1H), 4.49(dd, 1H), 6.8 (t, 1H), 6.75-6.88(m, 2H), 6.99 (m, 2H),7.05-7.21(m, 6H, 7.32 (d, 2H) Chiral 13

[R-(R*,R*)]-N-[5-[3-[[1-[4- (Difluoromethoxy)phenyl]-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide. SM2 507 6.4 - LC7 (270 MHZ, CDCl3) 2.31-2.46(m, 2H),2.46-2.60(m, 2H), 2.87(s, 3H), #2.95(m, 2H), 3.60(m, 1H), 3.84(t, 1H),4.5-5.0(broad, 4H), 6.50(t, 1H), 6.58(d, 1H), 6.69 (dd, 1H),6.99-7.11(m, 5H), 7.13-7.29(m, 5H) Chiral 14

[S-(R*,S*)]-N-[5-[3-[[10[4- (Difluoromethoxy)-3- methoxyphenyl]-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 537 20.5 - LC5 (270 MHz, CD3OD)2.51-2.80(m, 3H), 2.89(s, 3H), 2.93(dd, 1H), 3.19(dd, 1H), 3.40(dd,#1H), 3.80(s, 3H), 4.02(m, 1H), 4.45 (dd, 1H), 6.72(t, 1H), 6.78(d, 1H),6.85(m, 2H), 7.00(m, 3H), 7.06-7.23(m, 5H) Chiral 15

[S-(R*,S*)]-N-[5-[3-[[1-[3,4- Bis(difluoromethoxy)phenyl]-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 573 21.0 - LC5 (270 MHz, CD3OD)2.5-2.8 (m, 3H), 2.90(s, 3H), #2.97(dd, 1H), 3.16(t, 1H), 3.45(dd, 1H),4.03 (m, 1H), 4.50(dd, 1H), 6.83(t, 1H), 6.77(t, 1H), 6.8-6.9(m, 2H),6.95-7.06(m, 2H), 7.1-7.35 (m, 7H) Chiral 16

[S-(R*,S*)]-N-[5-[3-[[1-[3- (difluoromethoxy)-4- methoxyphenyl]-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:). SM1 537 20.0 - LC5 (270 MHz, CD3OD)2.5-2.8 (m, 3H), 2.91(s, 3H), 2.9(dd, overlapped with singlet, 1H),3.18(dd, 1H), #3.41(dd, 1H), 3.87(s, 3H), 4.04(m, 1H), 4.43 (dd, 1H),6.67(t, 1H), 6.80(d, 1H), 6.87(dd, 1H), 6.95-7.25 (m, 9H) Chiral 17

[S-(R*,S*)]-N-[5-[3-[[1-(1,3- Benzodioxol-5-yl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM3 485 19.3 - LC5 (270 MHz, CD3OD) 2.50-2.80(m, 3H), 2.87(dd,1H), 2.90(s, 3H), 3.18(dd, 1H), 3.36(dd, 1H), 4.03(m, 1H), 4.36(dd, 1H),5.97 (d, #2H), 6.65-6.86(m, 5H), 6.95-7.24(m, 6H) Chiral 18

[S-(R*,S*)]-N-[5-[3-[[1-(2,3- Dihydro-1,4-benzodioxin-6-yl)-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-foanmide, trifluoroacetate (1:1). SM1 499 18.8 - LC5 (270 MHz, CD3OD)2.50-2.80(m, 3H), 2.87(dd, 1H), 2.89(s, 3H), 3.18(dd, 1h), 3.33(dd, 1H),4.01(m, 1H), 4.22(s, 4H), 4.31 (dd, #1H), 6.68-6.88(m, 5H), 7.00(m, 2H),7.10-7.22(m, 4H) Chiral 19

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Diethoxyphenyl-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM1 529 20.9 - LC5 (270 MHz, CD3OD) 1.48-1.56(q, 6H),2.70-3.10(m, 4H), 3.03(s, 3H), 3.30-3.55(m, 2H), 4.11-4.21(m, 5H),4.45-4.55(dd H), 6.85- #7.05(m, 5H), 7.08-7.14(m, 2H), 7.20-7.35(m 4H)20

(2S)-N-[-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(4-methoxy-1- naphthalenyl)-2-phenylethyl]amino]propyl]phe- nyl]methanesulfonamide,trifluoroacetate(1:1). SM1 521 6.3 - LC2 (270 MHz, CD3OD) 2.35-2.96, (m,4H), 2.82 and 2.84(s, 3H), 3.27-3.48(m, 1H), #(m, 1H), 3.52-3.70 (m,1H), 3.81-4.08(m, 1H), 4.92 (s, 3H), 4.80-4.99(m, 1H), 5.30-5.48(br.s,1H), 6.52-6.70 (m, 2H), 6.91-7.10(m, 7H), 7.35-7.48(m, 2H), 7.66-7.90(m,2H), 8.16-8.29(m, 1H) 21

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(2- naphthalenyl)-2-phenylethyl]amino]propyl]phen- yl]methanesulfonamide,trifluoroacetate(1:1). SM1 491 6.1 - LC2 (270 MHz, CD3OD) 2.51-3.00(m,4H), 2.77 and 2.79(s, 3H), 3.21-3.41(m, 1H), 3.45-3.64(m, 1H),3.86-4.14(m, 1H), 4.53-4.68(m, 1H), 6.62-6.83(m, 2H), #(m, 2H),6.91-7.19(m, 7H), 7.41-7.55(m, 3H), 7.70-7.93(m, 4H) Chiral 22

[S-(R*,S*)]-N-[5-[3-[[2-(2- Chlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl)ami- no]-2-hydroxypropyl]-2-hydroxyphetnyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 53519.6 - LC5 (270 MHz, CD3OD) 2.50-2.80(m, 3H), 2.88(s, 3H), 2.95(dd, 1H),3.40(dd, 1H), 3.59(dd, 1H), 3.76(s, 6H), 4.06(m, 1H), 4.49 (dd, 1H),#6.70-7.17(m, 9H), 7.29(d, 1H) Chiral 23

[S-(R*,S*)]-N-[5-[3-[[2-(3- Chlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphentyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 53520.3 - LC5 (270 MHz, CD3OD) 2.50-2.80(m, 3H), 2.89(s, 3H), 2.90(dd, 1H),3.23(dd, 1H), 3.40(dd, 1H), 3.79(s, 6H), 4.04(m, 1H), #4.39 (dd, 1H),6.73-7.00(m, 6H), 7.00-7.20(m, 4H) Chiral 24

[S-(R*,S*)]-N-[5-[3-[[2-(4- Chlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 53520.7 - LC5 (270 MHz, CD3OD) 2.50-2.80(m, 3H), 2.88(s, 3H), 2.90(dd, 1H),3.23(dd, 1H), 3.39(dd, 1H), 3.78(s, 6H), 4.04(m, 1H), #4.36 (dd, 1H),6.73-6.90(m, 4H), 6.90-7.02(m, 3H), 7.06-7.20(m, 3H) Chiral 25

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2-(2-fluorophenyl)ethyl]amino]-2- hydroxypropyl]-2-hydroxyphentyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5194.7 - LC4 (300 MHz, CD3OD) 2.51-2.79(m, 3H), 2.90(s, 3H), 2.92(m, 1H),3.32(m, 1H), 3.45(dd, 1H), 3.79 (s, 3H), 3.81(s, 3H), 4.05 #(m, 1H),4.42(dd, 1H), 6.75-6.90 (m, 4H), 6.90-7.02(m, 4H), 7.11 (d, 1H), 7.19(m,1H) Chiral 26

[S-(R*,S*)]-N-[4-[3-[[1-(3,4- Dimethoxyphenyl)-2-(3-fluorophenyl)ethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 519 4.8 - LC4 (300 MHz, CD3OD)2.54(dd, 1H), 2.63(dd, 1H), 2.72(dd, 1H), 2.88(s, 3H), 2.89(m, 1H),3.33(t, 1H), 3.40 #(dd, 1H), 3.79 (s, 3H), 3.81(s, 3H), 4.03(m, 1H),4.38(dd, 1H), 6.74-6.94 (m, 8H), 7.10(s, 1H), 7.18(m, 1H) Chiral 27

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2-(4-fluorophenyl)ethyl]amino]-2- hydroxypropyl]-2-hydroxyphetnyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5194.8 - LC4 (300 MHz, CD3OD) 2.50-2.80(m, 3H), 2.90(s, 3H), 2.91(m, 1H),3.22(m, 1H), 3.39(dd, 1H), 3.80 (s, 3H), 3.82(s, 3H), #4.05(m, 1H),4.35(dd, 1H), 6.75-7.05 (m, 9H), 7.12(d, 1H) Chiral 28

[S-(R*,S*)]-N-[4-[3-[[1-(3,4- Dimethoxyphenyl)-2-(2-methylphenylethyl]amino]- 2-hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 515 5.5 - LC4 (300 MHz, CD3OD)2.15(s, 3H) 2.55(dd, 1H), 2.61-2.75(m, 2H), 2.89(m, 1H), 2.87(s, 3H),3.27(m, 1H), 3.37(dd, 1H) 3.74 (s, 3H), #3.78(s, 1H), 4.05(m, 1H),4.32(dd, 1H), 6.70-7.09 (m, 10H) Chiral 29

[S-(R*,S*)]-N-[4-[3-[[1-(3,4- Dimethoxyphenyl)-2-(3-methylphenyl)ethyl]amino]- 2-hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 515 5.3 - LC4 (400 MHZ, CDCl3)2.19(s, 3H), 2.45(m, 2H), 2.69(t, 1H), 2.83 (m, 4H), 3.18(t, 1H), 3.39(dd, 1H), 3.83(s, 6H), 4.10 =mx,1 (m, 1H), 4.21 #(m, 1H), 6.70(t, 4h),6.75(s, 1H), 6.79(s, 1H), 6.93 (d, 1H), 7.00(m, 3H), 7.37 (bs, 1H),8.89(bs, 1H), 9.02 (bs, 1H) Chiral 30

[S0(R*,S*)]-N-[4-[3-[[10(3,4- Dimethoxyphenyl)-2-(4-methylphenyl)ethyl]amino]- 2-hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 515 2.9 - LC1 (270 MHz, CD3OD)1.55-1.90(m, 2H), 2.22(s, 3H), 2.50-2.80(m, 2H), 2.88(s, 3H),3.40-3.50(m, 1H), 3.50-3.60(m, 1H), 3.78(s, 3H), #3.81(s, 3H),3.90-4.02(m, 1H), 4.30(dd, 1H), 6.70-7.00 (m, 9H), 7.10(d, 1H) Chiral 31

[S-(R*,S*)]-N-[5-[3-[[2-(2- Bromophenyl)-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 579, 5815.6 - LC4 (400 MHz, CD3OD) 2.56(dd, J=7.4, 13.7, 1H), 2.68(dd, J=10.8,12.5, 1H), 2.75(dd, J=6.0, 13.7, 1H), 2.88(s, 3H), #2.93(dd, J=2.3,12.7, 1H), 3.37(m, 1H), 3.57(dd, J=4.3, 13.1, 1H), 3.78(s, 3H), 3.79(s,3h), 4.05(m, 1h), 4.50(dd, J=4.3, 11.3, 1H), 6.71-6.93(m, 7H),7.05-7.10(m, 7H) Chiral 32

[S-(R*,S*)]-N-[5-[3-[[2-(3- Bromophentyl)-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphentyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 579,581 5.3 - LC4 (300 MHz, CD3OD) 2.50-2.80(m, 4H), 2.91(s, 3H), 3.10(dd,1H), 3.40(dd, 1H), 3.79(s, 3h), 3.81 (s, 3H), 4.05(dd, 1H), #4.39(dd,1H), 6.9-6.98(m, 6H), 7.09-7.38 (m, 4H) Chiral 33

[S-(R*,S*)]-N-[4-[3-[[2-(4- Bromophenyl)-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 579, 5815.9 - LC4 Chiral 34

[S-(R*,S*)]-N-[5-[3-[[2-[1,1′- Biphenyl]-2-yl-1-(3,4-dimethoxyphenyl)ethyl)ami- no]-2-hydroxypropyl]-2-hydroxyphentyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5776.3 - LC4 (300 MHz, CD3OD) 2.44-2.48(m, 2H), 2.68-2.76(m, 2H), 2.86(s,3H), 3.37(dd, 2h), 3.60(2, 3H), 3.80(s, 3h), 3.88(dd, 1H), 4.10 #(dd,1H), 6.38-6.52(m, 2H), 6.66-6.91(m, 3H), 7.96-7.37(m, 10H) Chiral 35

[S0(R*,S*)]-N-[4-[3-[[2-[1,1′- Biphenyl]-3-yl-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphetnyl]methanesul- =mx,1 fonamide, trifluoroacetate (1:1). SM1577 6.6 - LC4 (300 MHz, CD3OD) 2.46-2.48(m, 2H), 2.68-2.76(m, 2H),2.86(s, 3h), 3.37(m, 2H), 3.66(s, 3H), 3.80(d, 3H), 4.05(dd, 1H), 4.40#(dd, 1H), 6.78-7.24(m 15H) Chiral 36

[S-(R*,S*)]-N-[5-[3-[[2-[1,1′Biphentyl]-2-yl-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5776.5 - LC4 (300 MHz, CD3OD) 2.58(dd, 1H), 2.65-2.74(m, 2H), 2.89 (dd,1H), 2.89(s, 3H), 3.36(m, 1H), 3.45(dd, 1H), 3.78(s, 6H), #4.05(m, 1H),4.39(dd, 1H), 6.76 7.50(m, 15H) Chiral 37

[S-(R*,S*)]-N-[4-[3-[[2-(2,4- Dichlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 569, 5716.0 - LC4 (300 MHz, CD3OD) 2.52-2.82(m, 3H), 2.90(s, 3H), 2.94(m, 1H),3.38(m, 1H), 3.58(dd, 1h), 3.81 (s, 6H), 4.06 #(m, 1H), 4.46(dd, 1H),6.71-7.00(m, 6H), 7.05-7.12(m, 2H), 7.40(d, 1H) Chiral 38

[S-(R*,S*)]-N-[4-[3-[[2-(3,4- Dichlorophenyl)-1-)(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 569, 5716.1 - LC4 (300 MHz, CD3OD) 2.52-2.80(m, 3H), 2.90(s, 3H), 2.91(m, 1H),3.22(t, 1h), 3.38(dd, 1H), 3.81 (s, 3H), 3.83(s, 3H), 4.04 #(m, 1H),4.39(dd, 1h), 6.75-6.98 (m, 6H), 7.11(d, 1H), 7.20(d, 1h), 7.32(d, 1H)Chiral 39

[S-(R*,S*)]-N-[4-[3-[[2-(2,3- Dichlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 569, 5716.3 - LC7 (270 MHz, CD3OD) 1.60-1.90(m, 2H), 2.50-2.95(m, 2H), 2.88(s,3H), 3.40-3.50(m, 1H), 3.55-3.70(m, 1H), #3.80(s, 3H), 3.81 4.00-4.10(m,1H), 4.50 (dd, 1h), 6.70-6.90(m, 5H), 6.94(d, 1h), 7.04(t, 1H), 7.10 (d,1H), 7.35(d, 1H) Chiral 40

[S-(R*,S*)]-N-[5-[3-[[2-(2,5- Dichlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 569, 5716.4 - LC7 (270 MHz, CD3OD)1.60-1.90(m, 2H), 2.50-2.95(m, 2H), 2.88(s,3H), 3.40-3.60(m, 4H),3.80(s, 3H), 3.81(s, 3H), 4.00-4.10(m, 1H),4.50(dd, 1H), 6.70-6.90 (m, 4H), 6.95(dd, 2H), 7.10(d, 1H), 7.20(dd,1H), 7.30(d, 1H) Chiral 41

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2-[3-(trifluoromethyl)phen- yl]ethyl]amino]-2- hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 56920.9 - LC5 (270 MHz, CD3OD) 2.5-2.8(m, 3H), 2.88(s, 3H), 2.9(dd,overlapped with singlet, 1H), 3.3 (overlapped #solvent, 1H), 3.48(dd,1H), 3.78(s, 3h), 3.80 (s, 3H), 4.03(m, 1H), 4.42(dd, 1H), 6.7-7.0(m,5H), 7.10(d, 1H), 7.2-7.5(m 4H) Chiral 42

[S-(R*,S*)]-N-[4-[3-[[1-(3,4- Dimethoxyphenyl)-2-[3-(trifluoromethoxy)phenyl]eth- yl]amino]-2- hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 58521.2 - LC5 (270 MHz, CD3OD) 2.50-2.80 (m, 3H), 2.88(s, 3h), 2.90(dd,1H), 3.25(dd, 1H), 3.43(dd, 1H), 3.78(s, #3H), 3.80(s, 3H), 4.02 (m,1H), 4.39(dd, 1H), 6.72-71.7(m, 9H), 7.29(t, 1H) Chiral 43

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2-(1-naphthalenyl)ethyl]amino]- 2-hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 551 5.7 - LC4 Chiral 44

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2-(2-methoxyphenyl)ethyl]amino]- 2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 53118.7 - LC5 (270 MHz, CD3OD) 2.50-2.80(m, 3H), 2.88(s, 3H), 2.90(dd, 1H),3.15(dd, 1H), 3.45(dd, 1H), 3.77(s, 3H), 3.78(s, 3H), 3.79 #(s, 3H),4.02(m, 1H), 4.42(dd, 1H), 6.65-6.92(m, 8H), 7.09-7.19(m, 2H) 45

(2S)-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2-(3- methoxyphenyl)ethyl]ami-no]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide,trifluoroacetate (1:1). SM1 531 17.7 - LC5 46

(2S)-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2-(4- methoxyphenyl)ethyl]ami-no]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide,trifluoroacetate (1:1). SM1 531 17.6 - LC5 Chiral 47

[S-(R*,S*)]-N-[4-[3-[[2-(2- Chlorophenyl)-1-[4- (difluoromethoxy)-3-methoxyphenyl]ethyl]amino]- 2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5713.8 - LC3 (270 MHz, CD3OD) 2.52-2.80(m, 3H), 2.89(s, 3H), 3.01(dd, 1H),3.35(dd, 1h), 3.60(dd, 1H), 3.80(s, 3H), 4.06 #(m, 1H), 4.58 (dd, 1H),6.70(t, 1H), 6.75-6.95 (m, 4H), 7.03-7.21(m, 5H), 7.32 (d, 1H) Chiral 48

[S-(R*,S*)]-N-[5-[3-[[2-(3- Chlorophenyl)-1-[4- (difluoromethoxy)-3-methoxyphenyl]ethyl]amino]- 2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 57127.5 - LC6 (270 MHz, CD3OD) 2.51-2.80(m, 3H), 2.89(s, 3h), 2.95(dd, 1H),3.20(dd, 1H), 3.41(dd, 1H), 3.83(s, 3h), 4.04 #(m, 1H), 4.49 (dd, 1H),6.72(t, 1H), 6.75-6.96 (m, 4h), 7.04-7.20(m, 6H) Chiral 49

[S-(R*,S*)]-N-[4-[3-[[2-(4- Chlorophenyl)-1-[4- (difluoromethoxy)-3-methoxyphenyl]ethyl]amino]- 2-hydroxypropyl]-2- hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1). SM1 571 6.4 - LC4 (300 MHz, CD3OD)2.53-2.76(m, 2H), 2.89(s, 3H), 2.95(m, 1H), 3.16-3.44(m, 2h), 3.82(s,3H), 4.05(m, 1H), 4.44 #(dd, J=4.4, 4.05(m, 1H), 4.44(dd, J=4.4, 11.2,1h), 6.47-7.19(m, 11H) Chiral 50

[S-(R*,S*)]-N-[5-[3-[[1-[3,4- Bis(difluoromethoxy)phenyl]- 2-(2-chlorophenyl)ethyl]amino]- 2-hydroxypropyl]-2-hydroxyphenyl]kmethanesul- fonamide, trifluoroacetate (1:1). SM1 60727.6 - LC6 270 MHz, CD3OD) 2.52-2.79(m, 3H), 2.89(s, 3H), 3.02(dd, 1H),3.32(dd, 1H), 3.59(dd, 1H), 4.04(m, 1H), 4.60(dd, 1H), #6.72(t, 1H),6.83(t, 1H), 6.75-6.95 (m, 3H), 7.04-7.35(m, 7H) Chiral 51

[S-(R*,S*)]-N-[5-[3-[[1-[3,4- Bis(difluoromethoxy)phenyl]- 2-(3-chlorophenyl)ethyl]amino]- 2-hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 (605) 6.2 - LC4 (400 MHz, CDCl3)2.45(dd, 1H), 2.55(d, 1H), 2.72(t, 1H), 2.92 (s, 3H), 2.90(t, 1H),3.18(t, 1H), 3.65(dd, 1H), #3.70(dd, 1H), 4.159m, 1H), 4.30(dd, 1H),6.54 (t, 2H), 6.73(q, 2H), 6.78(d, 1H), 6.93(s, 1H), 6.98(d, 1H),7.07-7.30(m, 5H) Chiral 52

[S0(R*,S*)]-N-[5-[3-[[2-(4- Chlorophenyl)-1-[3,4-bis(difluoromethoxy)phenyl]eth- yl]amino]-2- hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 6076.7 - LC4 (300 MHz, CD3OD) 2.55-2.77(m, 2H), 2.91(s, 3H), 2.96-3.21(m,2H), 3.45(dd, J=4.3, 13.2, 1H), 4.05(m, 1H), #4.51(dd, J=4.3, 11.2, 1H),6.53-7.34(m, 12H) Chiral 53

[S-(R*,S*)]-N-[5-[3-[[2-(2- Chlorohenyl)-1-[3- (difluoromethoxy)-4-methoxyphenyl]ethyl]amino]- 2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5713.8 - LC3 (270 MHz, CD3OD) 2.51-2.79(m, 3H), 2.89(s, 3H), 2.95(dd, 1H),3.31(dd, 1H), 3.59(dd, 1H), 3.85(s, 3H), #4.04(m, 1H), 4.51 (dd, 1H),6.67(t, 1H), 6.75-6.97 (m, 3H), 6.98-7.21(m, 6H), 7.31 (d, 1H) Chiral 54

[S-(R*,S*)]-N-[4-[3-[[2-(3- Chlorophenyl)-1-[3- difluoromethoxy)-4-methoxyphenyl]ethyl]amino]- 2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5716.2 - LC4 300 MHz, CD3OD) 2.56(dd, 1H), 2.66(dd, 1H), 2.74(dd, 1H),2.90(s, 3H), 2.91(m, 1H), 3.17(t, 1H), #3.39(dd, 1H), 3.88 (s, 3H),4.02(m, 1H), 4.44(dd, 1H), 6.68(t, 1H), 6.79(d, 1H), 6.84(d, 1H),6.90(m, 1H), 7.03-7.20(m, 7H) Chiral 55

[S0(R*,S*)]-N-[5-[3-[[2-(4- Chlorophenyl)-1-[3- (difluoromethoxy)-4-methoxyphenyl]ethyl]amino]- 2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 (569)5.8 - LC4 (400 MHz, CDCl3) 2.39(dd, 1H), 2.45(d, 1H), 2.66(t, 1H),2.84(s, 3H), 2.90(t, 1H), 3.12(t, 1H), #3.83(s, 3H), 4.15(t, 1H),6.54(t, 1H), 6.67(q, 2H), 6.80(d, 2H), 6.90(d, 1H), 6.97(s, 1H), 7.08(d,2H) 7.14(s, 1H), 7.35(s, 1H), 8.88(bs, 1H), 9.29(bs, 1H) 56

(2S)-N-[5-[3-[[1-(4- Cyanophenyl-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM5B 466 3.1 - LC3 57

(2S)-N-[5-[3-[[1-(3- Cyanophenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM5B 466 3.1 - LC3 58

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(3- hydroxyphenyl)-2-phenylethyl]amino]propyl]phen- yl]methanesulfonamide,trifluoroacetate(1:1). SM5B 457 3.0 - LC3 59

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(4- hydroxyphenyl)-2-phenylethyl]amino]propyl]phen- yl]methanesulfonamide,trifluoroacetate(1:1). SM5B 457 2.9 - LC3 60

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-[3- (phenylmethoxy)phenyl]-2-phenylethyl]amino]propyl]phen- yl]methanesulfonamide,trifluoroacetate(1:1). SM5A 547 4.1 - LC3 61

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-[4- (phenylmethoxy)phenyl]-2-phenylethyl]amino]propyl]phen- yl]methanesulfonamide,trifluoroacetate(1:1). SM5B 547 4.1 - LC3 62

(2S)-N-[4-[1-[[2-Hydroxy-3- [4-hydroxy-3- [(methylsulfonyl)amino]phe-nyl]propyl]amino]-2- phenylethyl]phenyl]aceta- mide,trifluoroacetate(1:1). SM5B 498 3.0 - LC3 63

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-[4-(2- hydroxyethoxy)henyl]-2-phenylethyl]amino]propyl]phe- nyl]methanesulfonamide,trifluoroacetate(1:1). SM5B 501 3.0 - LC3 64

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-[3-(2- hydroxyethoxy)phenyl]-2-phenylethyl]amino]propyl]phe- nyl]methanesulfonamide,trifluoroacetate(1:1). SM5B 501 3.1 - LC3 65

(2S)-[4-[1-[[2-Hydroxy-3-[4- hydroxy-3- [(methylsulfonyl)amino]phe-nyl]propyl]amino]-2- phenylethyl]phenyl]phos- phonic acid diethyl ester,trifluoroacetate(1:1). SM5B 577 3.4 - LC3 66

(2S)-N-[5-[3-[[1-[4-[2- (Diethylamino)ethoxy]phen-yl]-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:2). SM5A 556 2.4 - LC3 67

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(4-hydroxy-3- methylphenyl-2-phenylethyl]amino]propyl]phe- nyl]methanesulfonamide,trifluoroacetate(1:1). SM5B 471 3.2 - LC3 Chiral 68

[S-(R*,S*)]N-[2-Hydroxy-5- [2-hydroxy-3-[[1-[4- methoxy-3-(phenylmethoxy)phenyl]-2-phenylethyl]amino]propyl]pheny]methanesulfonamide,trifluoroacetate(1:1). SM1 577 23.9 - LC5 (270 MHz, CD3OD) 2.48-2.78(m,3H), 2.83(dd, 1H), 2.88(s, 3H), 3.09(dd, 1H), #3.3(dd, 1H), 3.82 (s,3H), 4.00(m, 1H), 4.29(dd, 1H), 5.09(s, 2H), 6.69-6.88(m, 6 or 7H),6.98(d, 1H), 7.11(m, 4H), 7.30-7.45(m, 5 or 4H) Chiral 69

[S-(R*,S*)]-N-[5-[3-[[1-(3- Fluoro-4-methoxyphenyl)-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 489 23.4 - LC6 (270 MHz, CD3OD)2.50-2.79(m, 3H), 2.89(s, 3H), 2.89(dd, 1H), 3.18(dd, 1H), 3.39(dd, 1H),#3.84(s, 3H), 4.01(m, 1H), 4.40 (dd, 1H), 6.79(d, 1H), 6.84(dd, 1H),6.92-7.08(m, 4H), 7.09-7.22(m, 5H) Chiral 70

[S-(R*,S*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1[3- methoxy-4-(2,2,2-trifluoroethoxy)phenyl]-2- phenylethyl]amino]propyl]phe-nyl]methanesulfonamide, trifluoroacetate(1:1). SM1 569 21.3 - LC5 (270MHz, CD3OD) 2.55-3.20(m, 4H0, 3.00(s, 3H), 3.20-3.68(m, 2H), 3.81-#4.05(m, 1H), 3.89(s, 3H), 4.08-4.28(m, 1H), 4.45-4.72(m, 3H),6.80-7.45(m, 11H) Chiral 71

[S-(R*,S*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1-[4- methoxy-3-(2,2,2-trifluoroethoxy)phenyl]-2- phenylethyl]amino]propyl]phe-nyl]methanesulfonamide, trifluoroacetate(1:1). SM1 569 21.1 - LC5 (270MHz, CD3OD) 2.50-2.95(m, 4H), 2.89(s, 3H), 3.15-3.43(m, 2H), 3.84 #(s,3H), 3.98-4.10(m, 1h), 4.30-4.50(m, 3H), 6.75-7.20(m, 11H) 72

(2S)-N-[4-[3-[[1-(3-Chloro-4- hydroxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM5B 491 3.1 - LC3 Chiral 73

[-(R*,S*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1-(3-hydroxy-4-methoxyphenyl)-2- phenylethyl]amino]pro-pyl]phenyl]methanesulfonamide, trifluoroacetate(1:1). SM1 487 20.1 - LC6(270 MHz, CD3OD) 2.48-2.78(m, 3H), 2.85(dd, 1H), 2.88(s, 3H), 3.19(dd,1H), 3.34(dd, 1H), 3.82(s, 3H), #4.01(m, 1H), 4.28 (dd, 1H), 6.63(dd,1H), 6.74-6.88(m, 4H), 6.99(m, 2H), 7.07-7.22(m, 4H) 74

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(3-hydroxy-4- methoxyphenyl)-2-phenylethyl]amino]propyl]phe- nyl]methanesulfonamide,trifluoroacetate(1:1). SM5B 487 3.1 - LC3 75

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(4-hydroxy-3- methoxyphenyl)-2-phenylethyl]amino]propyl]phen- yl]methanesulfonamide,trifluoroacetate(1:1). SM5B 487 2.9 - LC3 76

(2S)-2-[4-[1-[[2-Hydroxy-3- [4-hydroxy-3- [(methysulfonyl)amino]phe-nyl]propyl]amino]-2- phenylethyl]-2- methoxyphenoxy]acetic acid,trifluoroacetate(1:1). SM5B 545 3.0 - LC3 77

(2S)-N-[5-[3-[[1-(3-Fluoro-4- hydroxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM5B 475 3.0 - LC3 78

(2S)-N-[5-[3-[[1-(3,4- Dichlorophenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM5A 509, 511 3.9 - LC3 79

(2S)-N-[5-[3-[[1-(1,3- Benzodioxol-4-yl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM5A 485 3.4 - LC3 80

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1- (3,4,5,6,8,9,11,12-octahydro-1,4,6,10,13- benzopentaoxacyclopenta decin-15-yl)-2-phenylethyl]amino]propyl]phenyl]methanesulfonamide,trifluoroacetate(1:1). SM5A 631 3.3 - LC3 81

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(4-methoxy-3- methylphenyl)-2-phenylethyl]amino]propyl]phe- nyl]methanesulfonamide,trifluoroacetate(1:1). SM5A 485 3.7 - LC3 82

(2S)-N-[5-[3-[[1-[4-Fluoro-3- (trifluoromethyl)phenyl]-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM5A 527 3.8 - LC3 83

(2S)-N-[5-[3-[[1-(3,5- Dimethoxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM5A 501 3.5 - LC3 Chiral 84

[S-(R*,S*)]-N-[4-[3-[[1-(3- Bromo-4-methoxyphenyl)-2phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 549, 551 3.7 - LC3 (370 MHz,CD3OD) 2.50-2.79(m, 3H), 2.9(m, 1H), 2.89(s, 3H), 3.19(dd, 1H), 3.40#(dd, 1h), 3.86(s, 3H), 4.019m, 1H), 4.40 (dd, 1H), 6.77-6.88(m, 2H),6.93-7.03(m, 3H), 7.10-7.33(m, 5H), 7.55(m, 1H) Chiral 85

[S-(R*,S*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1-(3,4,5-trimethoxyphenyl)-2- phenylethyl]amino]propyl]phe-nyl]methanesulfonamide trifluoroacetate(1:1). SM1 531 3.3 - LC3 (270MHz, CD3OD) 2.52-2.80(m, 3H), 2.88(s, 3H), 2.93(dd, 1H), 3.19(dd, 1H),3.39 #(dd, 1H), 3.73(s, 3H), 3.76(s, 6H), 4.03 (m, 1H), 4.38(dd, 1H),6.59(s, 2H), 6.79(d, 1H), 6.87(dd, 1H), 7.01(m, 2H), 7.11(d, 1H),7.15-7.23(m, 3H) Chiral 86

[S-(R*,S*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1-(7-methoxy-1,3-benzodioxol-5- yl)-2- phenylethyl]amino]propyl]phe-nyl]methanesulfonamide, trifluoroacetate(1:1). SM1 515 3.4 - LC3 (270MHz, CD3OD) 2.51-2.79(m, 3H), 2.89(s, 3H), 2.89(dd, 1H), 3.16(dd, 1H),3.35 #dd, 1H), 3.79(s, 3h), 4.02(m, 1H), 4.33 (dd, 1H), 5.949dd, 2H),6.49 (dd, 2H), 6.79(d, 1H), 6.85(dd, 1H), 7.01(m, 2H), 7.09-7.25(m, 4H)87

(2S)-N-=8 5-[3-[[1-(3-Chloro- 4,5-dimethoxyphenyl)-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM5A 535 3.6 - LC3 88

(2S)-N-[5-[3-[[1-(2-Chloro- 3,4-dimethoxyphenyl)-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul- amide,trifluoroacetate (1:1). SM5 A 535 3.5 - LC3 89

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(4-hydroxy-3,5-dimethoxyphenyl)-2- phenylethyl]amino]propyl]phe-nyl]methanesulfonamide, trifluoroacetate(1:1). SM5B 515 3.4 - LC3 90

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(4-hydroxy-3,5-dimethoxyphenyl)-2- phenylethyl]amino]propyl]phe-nyl]methanesulfonamide, trifluoroacetate(1:1). SM5B 517 2.9 - LC3 91

(2S)-N-[5-[3-[[1-(3,5- Dichloro-4-hydroxyphenyl)-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM5B 525, 527 3.3 - LC3 92

(2S)-N-[5-3-[[1-(3-Chloro-4- hydroxy-5-methoxyphenyl)-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM5B 521 3.2 - LC3 93

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(3-hydroxy-4,5-dimethoxyphenyl)-2- phenylethyl]amino]propyl]phe-nyl]methanesulfonamide, trifluoroacetate(1:1). SM5B 517 3.0 - LC3 94

(2S)-N-[5-[3-[[1-(3,5- Dihydroxy-4- methoxyphenyl)-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM5B 503 2.8 - LC3 95

(2S)-N-[5-[3-[[1-(2-Bromo- 4,5-dimethoxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fon amide, trifluoroacetate(1:1). SM5A 579, 581 3.6 - LC3 96

(2S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[1-(7-methoxy-1,3-benzodioxol-5-yl)-2- phenylethyl]amino]propyl]phe-nyl]methanesulfonamide, trifluoroacetate(1:1). SM5A 515 3.4 - LC3 97

(2S)-N-[5-[30[[1-(6-Chloro- 1,3-benzodioxol-5-yl)-2-phenylethyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM5A 519 3.6 - LC3 98

[S0(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-3- phenylpropyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM1 515 5.8 - LC4 (300 MHz, CD3OD) 2.29-2.79(m, 8H0, 2.84(s, 3H),3.84(s, 3H), 3.85(s, 3H), 3.93-4.09(m, 2H), 6.76-7.26(m, 11H) 99

(2S)-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-3- phenylpropyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM1 515 5.5 - LC4 Chiral 100

[S-(R*,S*)]-N-[4-[30[[1-[3,4- Bis(difluoromethoxy)phenyl]-3-phenylpropyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 587 23.3 - LC5 (270 MHz, CD3OD)2.2-2.6(m, 4H), 2.71(dd, 1H), 2.88(s, 3H), 2.9(dd, overlapped with#singlet, 1H), 3.46(m, 1H), 3.57(m, 1H), 3.95(m, 1H), 4.18(dd, 1H), 6.756.85(m, 2H)), 6.86(t, 1H), 6.92 (t, 1H), 7.0-7.3(m, 6H), 7.3-7.5 (m, 3H)Chiral 101

]S-(R*,S*)]-N-[5-[3-[[1-[4- (Difluoromethoxy)-3- methoxyphenyl]-3-phenylpropyl]amino]-2- hydroxypropyl]-2- hydroxyphenyl]methanesul-fonamide, trifluoroacetate (1:1). SM1 551 22.5 - LC5 (270 MHz, CD3OD)2.27-2.63(m, 6H), 2.70(dd, 1H), 2.86(s, 3H), 2.88(dd, 1H), 3.91(s, 3h),3.94 (m, #1H), 4.12(dd, 1H), 6.78(d, 1H), 6.79(t, 1H), 6.83(dd, 1H),6.97-7.30(m, 9H) Chiral 102

[S-(R*,S*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1-(3- methoxyphenyl)-3-phenylpropyl]amino]propyl]phe- nyl]methanesulfonamide,trifluoroacetate(1:1). SM1 485 21.4 - LC5 (270 MHz, CD3OD) 2.27-2.61(m,6H), 2.69(dd, 1H), 2.85(dd, 1h), 2.87(s, #3H0, 3.83(s, 3h), 3.97(m, 1H),4.11(dd, 1H), 6.78 (d, 1H), 6.82(dd, 1H), 6.95-7.30 (m, 9H), 7.39(m, 1H)Chiral 103

[S-(R*,S*)]-N-[2-Hydroxy-5- [2-hydroxy-3-[[1-(4- methoxyphenyl)-3-phenylpropyl]amino]propyl]phe- nyl]methanesulfonamide,trifluoroacetate(1:1). SM1 485 21.6 - LC5 (270 MHz, CD3OD) 2.27-2.60(m,6H), 2.70(dd, 1H), 2.80(dd, 1H), 2.87(s, #3H), 3.83(s, 3h), 3.97(m, 1H),4.09(dd, 1H), 6.79 (d, 1H), 6.83(dd, 1H), 7.01(d, 2H), 7.04-7.29(m, 6H),7.32(d, 2H) Chiral 104

[S0(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-3-[2-(trifluoromethyl)phenyl]pro- pyl]amino]-2- hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5836.3 - LC4 (300 MHz, CD3OD) 2.30-2.40(m, 2H), 2.41-2.86(m, 6H), 2.85(s,3H), 3.86(s, 3H), 3.87(s, 3H), 4.00 #(dd, 1H), 4.21(dd, 1H),6.75-7.10(m, 6H), 7.26-7.65(m, 4H) Chiral 105

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-3-[3-(trifluoromethyl)phenyl]pro- pyl]amino]-2- hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5836.4 - LC4 (300 MHz, CD3OD) 2.37-2.40(m, 12H), .250-2.60(m, 4H), 2.75(dd, 1H)), 2.81(dd, 1H), 2.86(s, 3H), 3.84 #(s, 3H), 3.86(s, 3H),3.98(dd, 1H), 4.10(dd, 1H), 6.75-7.10(m, 6H), 7.26-7.48(m, 4H) Chiral106

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-3-[4-(trifluoromethyl)phenyl]pro- pyl]amino]-2- hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5826.6 - LC4 (300 MHz, CD3OD) 2.37-2.40(m, 2H), 2.50-2.60(m, 4H), 2.75 (dd,1H), 2.81(dd, 1H), 2.85(s, 3H), 3.84 #(s, 3H), 3.86(s, 3H), 3.98(dd,1H), 4.10(dd, 1H), 6.75-7.10(m, 6H), 7.26(d, 2H), 7.56(d, 2H) Chiral 107

[S-(R*,S*)]-N-[5-[3-[[3-(2- Chlorophenyl)-1-(3,4-dimethoxyphenyl)propyl]a- mino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroaceate (1:1). SM1 549 6.2 -LC4 (300 MHz, CD3OD) 2.31-2.89(m, 8H), 2.89(s, #3H), 3.85(s, 3h),3.87(s, 3H), 4.00(m, 1H), 4.18 (m, 1H), 6.79(d, 1H), 6.85(dd, 1H),6.98(s, 2H), 7.08(s, 2H), 7.12-7.21(m, 3H), 7.32(dd, 1H) Chiral 108

[S-(R*,S*)]-N-[5-[3-[[3-(4- Chlorophenyl)-1-(3,4-dimethoxyphenyl)propyl]a- mino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 5496.4 - LC4 (300 MHz, CD3OD) 2.30-2.78(m, 8H0, 2.86(s, 3H), 3.84(s, 3H),3.85(s, 3H), 3.92(m, 1H), 4.1 (m, 1H), 6.76-7.25(m, 10H) Chiral 109

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-4- phenylbutyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM1 529 6.5 - LC7 (270 MHz, CD3OD) 1.25-1.65(m, 2H), 1.9-2.1(m,2H), 2.45-2.85 (m, 4H), 2.89 #s. 3H), 3.79(s, 3H), 3.85(s, 3H),3.89-4.02(m, 1H), 4.05-4.12(dd, 1H), 6.75-6.98(m, 5H), 7.06-7.25(m, 6H)110

(2S)-N-[5-[3-[[Bis[4- (difluoromethoxy)phenyl]meth- yl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM1 559 20.7 LC5 (270 MHz, CD3OD) 2.60(dd, 1H), 2.73(dd, 1H),2.91(s, 3H), 2.80-3.05(m, 2H), #4.10(m, 1H), 5.60(s, 1H), 6.79(d, 1H),6.85 (t, 1H), 6.86(t, 1H), 6.87(dd, 1H), 7.10-7.30(m, 5H), 7.45-7.57(m,4H) Chiral 111

[S-(R*,S*)]-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]propanesul- fonamide, trifluoroacetate(1:1). SM1 529 20.2 - LC5 (400 MHz, CDOD) 0.99(t, 3H), 1.82(m, 2H),2.54(dd, 1H), 2.63 (dd, 1H), 2.72 #(dd, 1H), 2.88 (dd, 1H), 2.9-3.0(m,2H), 3.20 (dd, 1H), 3.38(dd, 1H), 3.78 (s, 3H), 3.81(s,3H), 4.02(m, 1H),4.35(dd, 1H), 6.7-6.8(m, 3H), 6.8-6.9(m, 2H), 6.99(d, 2H), 7.1-7.2(m,4H) Chiral 112

[S-(R*,S*)]-N-[4-[3-[[1-(3,4- Dimethoxyphenyl)-2- phenylethyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]butanesulfo- namide, trifluoroacetate(1:1). SM1 543 21.6 - LC5 (400 MHz, CD3OD) 0.90(t, 3H), 1.38(m, 2H),1.78(m, 2H), 2.54 (dd, 1H), 2.63 #(dd, 1H), 2.72 (dd, 1H), 2.90(dd, 1H),2.98 (m, 2H), 3.20(dd, 1H), 3.38 (dd, 1H), 3.78(s, 3h), 3.81 (s, 3H),4.02(m, 1H), 4.36 (dd, 1H), 6.7-6.9(m, 5H), 6.99 (d, 2H), 7.1-7.2(m, 4H)113

N-[2-Hydroxy-5-]2-hydroxy- 3-[[(4- methoxyphenyl)methyl]ami-no]propyl]phenyl]methane- sulfonamide, trifluoroacetate(1:1). SM4B 38113.4 - LC5 (270 MHz, CD3OD) 2.63-3.3(m, 8H), 2.90(s, 3H), 4.00(m, 1H),6.75-7.00(m, 5H), 7.21(d, 1H) Chiral 114

(S)-N-[5-[3-[[(3,4- Dimethoxyphenyl)methyl]a- mino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). Sm5C 4112.3 - LC3 (270 MHz, CD3OD) 2.59-3.04(m, 4H), 2.90(s, 3H), 3.83(s, 6H),4.01(m, 1H), 4.11(s, 2h), 6.81 (d, 1H), 6.91(dd, 1H), 6.96(s, 2H),7.04(s, 1H), 71.7(d, 1H) 115

(2S)-N-[5-[3-[[1-(3,4- Dimethoxypehnyl)ethyl]ami-no]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide,trifluoroacetate (1:1). SM5C 425 2.4 - LC3 116

(2S)-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-3- butenyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifluoroacetate(1:1). SM5A 451 2.8 LC3 117

(2S)-N-[5-[3-[[1-(3,4- Dimethoxyphenyl)-3- methyl-3-butenyl]amino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide, trifloroacetate(1:1). SM5B 465 3.0 - LC3 Chiral 118

[S-(R*,S*)]-N-[5-[3-[[3- Cyclohexyl-1-(3,4- dimethoxyphenyl)propyl]a-mino]-2-hydroxypropyl]-2- hydroxyphenyl]methanesul- fonamide,trifluoroacetate (1:1). SM1 521 6.5 - LC7 (270 MHz, CD3OD) 0.70-0.95(m,2H), 1.02-1.30(m, 6H), 1.57-1.75(m, 5H), #1.90-2.10(m, 1H), 2.45-2.85(m,5H), 2.89(s, 3H), 3.84(s, 3H), 3.85(s, 3H), 3.90-4.10(m, 2H),6.75-7.00(m, 5H), 7.10(d, 1H) Chiral 119

(S)-N-[2-Hydroxy-5-[2- hydroxy-3-[(2- phenylethyl)amino]propyl]phe-nyl]methanesulfonamide, trifluoroacetate(1:1). SM1 365 2.1 - LC1 (270MHz, CD3OD) 2.70-3.00(m, 8H), 3.08(s, 3H), 4.03(m, 1H), 6.95(d, 1H),7.05(d, 1H), 7.30-7.50(m, 6H) 120

N-[5-[3-[[2-(3,4- Dimethoxyphenyl)ethyl]ami- no]-2-hydroxypropyl]-2-hydroxyphenyl]methanesul- fonamide, trifluoroacetate (1:1). SM4B 42513.7 - LC5 (270 MHz, CD3OD) 2.65(dd, 1H), 2.70-2.90(m, 2H), 2.91(s, 3H),2.97(dd, #1H), 3.81(s, 3H), 4.01(m, 1H), 4.11(s, 2H), 6.81 (d, 1H),6.86-7.00(m, 3H), 7.19 (d, 1H), 7.33(d, 2H) Chiral 121

(S)-N-[2-Hydroxy-5-[2- hydroxy-3-[[2-(4- phenoxyphenylethyl]ami-no]propyl]phenyl]methanesul- fonamide, trifluoroacetate (1:1). SM1 4572.9 - LC1 (270 MHz, CD3OD) 2.80(m, 2H), 3.03(s, 3H), 3.05(m, 2H),3.15-3.40(m, 4H), #4.12(m, 1H), 6.90 (d, 1H), 7.05(m, 6H), 7.20(t, 1H),7.30(d, 2H), 7.43(t, 2H) 122

N-[4-[2-[[2-Hydroxy-3-[4- hydroxy-3- [(methylsulfonyl)amino]phe-nyl]propyl]amino]ethyl]phe- nyl]benzenesulfonamide,trifluoroacetate(1:1). SM4A 520 4.4 - LC4 (270 MHz, CD3OD) 2.60-2.80(m,2H), 2.80-3.00(m, 3H), 2.89(s, 3H), 3.00-31.9 #(m, 3H), 3.99(, 1H),6.82(d, 1H0, 6.92(dd, 1H), 7.00-7.15(m, 4H), 7.19(d, 1H), 7.40-7.59(m,3H), 7.73(d, 2H) Chiral 123

(SO-N-[4-[2-[[2-Hydroxy-3- [4-hydroxy-3- [(methylsulfonyl)amino]phe-nyl]propyl]amino]ethyl]phe- nyl]-4-(1- methylethyl)benzenesulfon- amide,trifluoroacetate (1:1). SM1 562 2.9 - LC1 (270 MHz, CD3OD) 1.37(d, 6H),2.78-3.35(m, 8H), 3.07(s, 3H), 3.49(m, 1H), #4.15(m, 1H), 6.97 (d, 1H),7.10(dd, 1H), 7.23(m, 4H), 7.35(d, 1H), 7.50(d, 2H), 7.83(d, 2H)

[0076] For the Examples employing methods SM1, SM2, SM3, SM4A, and SM4B,amines H₂NCH(A) (CH₂)_(m)B were generally prepared by the methodsdescribed in U.S. patent application Ser. No. 08/346,543 filed Dec. 2,1994, or are known in the art. Examples 122 and 123 were prepared withamines available by the methods described in PCT applications WO95/29159 and EP 611003.

[0077] Modifications to the described methods were made in the synthesesof the following Examples: For Example 73 prepared by SM1, a benzylether was used to protect the phenolic hydroxyl group in amine H₂NCH(A)(CH₂)_(m)B until after coupling and amide reduction, when the benzylether was removed by catalytic hydrogenation. For Example 76 prepared bySM5B, the aldehyde ACHO used to form the resin-bound imine was4-methoxy-3-(methoxycarbonylmethoxy)-benzaldehyde. Subsequent tocleavage from the resin, the methyl ester was saponified. For Examples2, 4, 9 and 11, prepared by SM3 and for Example 13 prepared by SM2, theenantiomer of the intermediate methyl2,3-dihydroxy-3-(4-benzyloxy-3-(methylsulfonyl)aminophenyl)propanoatewas prepared by using (DHQ)₂PHAL instead of (DHQD)₂PHAL. All subsequentintermediates in the syntheses of these Examples contained R hydroxylstereocenters.

What is claimed is:
 1. A compound of the formula

or a pharmaceutically acceptable salt thereof, or stereoisomers thereof, wherein R¹ is lower alkyl, aryl or arylalkyl; A is hydrogen or

B is hydrogen, alkyl, alkenyl, or

but when A is hydrogen, B may only be

R², R^(2′), R^(2″), R³, R^(3′) and R^(3″) are independently hydrogen, hydroxy, alkoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, aryloxy, arylalkoxy, hydroxyalkoxy, lower alkyl, trifluoromethyl, halogen, cyano, alkylthio, alkylsulfinyl, alkylsulfonyl, -(CH₂)_(n)NR⁴COR⁵, -CONR⁴R^(4′), -CO₂R⁵, -NR⁴SO₂R¹, -NR⁴R^(4′), -OCH₂CH₂NR⁴R^(4′), -OCH₂CONR⁴R^(4′), -OCH₂CO₂R⁴, -PO₃R⁴R^(4′) or aryl; or R² and R^(2′) or R³ and R^(3′) may together form a carbocycle or heterocycle; m is 0−3; n=0−3; R⁴ and R^(4′) are independently hydrogen or lower alkyl; and R⁵ is lower alkyl.
 2. The compound as defined in claim 1 wherein A is


3. The compound as defined in claim 1 wherein -(CH₂)_(m)-B is


4. The compound as defined in claim 1 wherein R¹ is alkyl.
 5. The compound as defined in claim 1 wherein the hydroxyl stereocenter has the S configuration.
 6. The compound as defined in claim 1 wherein the amino stereocenter has the R configuration.
 7. The compound as defined in claim 1 wherein R¹ is CH₃, the hydroxyl stereocenter has the S configuration, the amino stereocenter has the R configuration, m is 1, A is and B is


8. The compound as defined in claim 1 which is [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-phenyl-ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methane-sulfonamide, or its trifluoroacetate (1:1) salt.
 9. The compound as defined in claim 1 which is [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl-2-phenyl-ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [R- (R*,R*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [R- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); (1R)-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-phenyl-ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methane-sulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-phenyl-ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methane-sulfonamide, trifluoroacetate (1:1); (2S) -N-[2-hydroxy-5-[2-hydroxy-3-[[1-(2-methoxy-phenyl)-2-phenylethyl]amino]propyl]phenyl]methane-sulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(3-methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); [R- (R*,R*)]-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(3-methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(4-methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); [R- (R*,R*)]-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(4-methoxyphenyl) -2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(4-(difluoromethoxy)phenyl]-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [R- (R*,R*)]-N-[5-[3-[[1-[4-(difluoromethoxy)phenyl]-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide; [S- (R*,S*)]-N-[5-[3-[[1-[4-(difluoromethoxy)-3-methoxyphenyl]-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-[3,4-bis(difluoromethoxy)-phenyl]-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-[3-(difluoromethoxy)-4-methoxyphenyl]-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(1,3-benzodioxol-5-yl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxy-phenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-diethoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(4-methoxy-1-naphthalenyl)-2-phenylethyl]amino]propyl]phenyl]methane-sulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(2-naphthalenyl)-2-phenylethyl]amino]propyl]phenyl]methanesulfonamide, trifluordacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(2-chlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(3-chlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(4-chlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(2-fluorophenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(3-fluorophenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(4-fluorophenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(3-methylphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(4-methylphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(2-bromophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(3-bromophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(4-bromophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-[1,1′-biphenyl]-2-yl-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-[1,1′-biphenyl]-3-yl-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-[1,1′-biphenyl]-4-yl-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(2,4-dichlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(3,4-dichlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(2,3-dichlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(2,5-dichlorophenyl)-1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-[3-(trifluoromethyl)phenyl]ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-[3-(trifluoromethoxy)phenyl]ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(1-naphthalenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(3-methoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-(4-methoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(2-chlorophenyl)-1-(4-(difluoromethoxy)-3-methoxyphenyl]ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, [S- (R*,S*)]-N-[5-[3-[[2-(3-chlorophenyl)-1-]4-(difluoromethoxy)-3-methoxyphenyl]ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(4-chlorophenyl)-1(4-(difluoromethoxy)-3-methoxyphenyl]ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-[3,4-bis(difluoromethoxy)-phenyl]-2-(2-chlorophenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-[3,4-bis(difluoromethoxy)-phenyl]-2-(3-chlorophenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(4-chlorophenyl)-1-[3,4-bis(difluoromethoxy)phenyl]ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(2-chlorophenyl)-1-[3-(difluoromethoxy)-4-methoxyphenyl]ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(3-chlorophenyl)-1-(3-(difluoromethoxy)-4-methoxyphenyl]ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[2-(3-chlorophenyl)-1-[3-(difluoromethoxy)-4-methoxyphenyl]ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(4-cyanophenyl)-2-phenylethyl]-amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(4-cyanophenyl)-2-phenylethyl]-amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(3-hydroxyphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(4-hydroxyphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-[3-(phenylmethoxy)phenyl[-2-phenylethyl]amino]propyl]-phenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-[4-(phenylmethoxy)phenyl]-2-phenylethyl]amino]propyl]-phenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[4-[1-[[2-hydroxy-3-[4-hydroxy-3-[(methylsulfonyl)amino]phenyl]propyl]amino]-2-phenylethyl]phenyl]acetamide, trifluoroacetate (: 1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-[4-(2-hydroxyethoxy)phenyl]-2-phenylethyl]amino]propyl[-phenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-[3-(2-hydroxyethoxy)phenyl]-2-phenylethyl]amino]propyl]-phenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-[4-[1-[[2-hydroxy-3-[4-hydroxy-3-[(methylsulfonyl)amino]phenyl]propyl]amino]-2-phenylethyl]phenyl]phosphonic acid diethyl ester, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-[4-[2-(diethylamino)ethoxy]phenyl]-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:2); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(4-hydroxy-3-methylphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*))-N-[2-hydroxy-5-[2-hydroxy-3-[[1-[4-methoxy-3-(phenylmethoxy)phenyl]-2-phenylethyl]amino]-propyl]phenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3-fluoro-4-methoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[2-Hhydroxy-5-[2-hydroxy-3-[[1-[3-methoxy-4-(2,2,2-trifluoroethoxy)phenyl]-2-phenylethyl]-amino]propyl]phenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-(2-hydroxy-5-[2-hydroxy-3-[[1-[4-methoxy-3-(2,2,2-trifluoroethoxy)phenyl]-2-phenylethyl]-amino]propyl]phenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3-chloro-4-hydroxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(3-hydroxy-4-methoxyphenyl)-2-phenylethyl]amino]propyl]-phenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(3-hydroxy-4-methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(4-hydroxy-3-methoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-2-[5-[1-[[2-hydroxy-3-[4-hydroxy-3-[(methylsulfonyl)amino]phenyl]propyl]amino]-2-phenylethyl]-2-methoxyphenoxy]acetic acid, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3-fluoro-4-hydroxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,4-dichlorophenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(1,3-benzodioxol-4-yl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-benzopenta-oxacyclopentadecin-15-yl)-2-phenylethyl]amino]propyl]-phenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(4-methoxy-3-methylphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-[4-fluoro-3-(trifluoromethyl)-phenyl]-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,5-dimethoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3-bromo-4-methoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(3,4,5-trimethoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(7-methoxy-1,3-benzodioxol-5-yl)-2-phenylethyl]amino]propyl]-phenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3-chloro-4,5-dimethoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfon amide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(2-chloro-3,4-dimethoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfon amide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(7-methoxy-1,3-benzodioxol-4-yl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(4-hydroxy-3,5-dimethoxyphenyl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,5-dichloro-4-hydroxyphenyl)-2-phenylethyl]amino[-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3-chloro-4-hydroxy-5-methoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,5-dihydroxy-4-methoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(2-bromo-4,5-dimethoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfon amide, trifluoroacetate (1:1); (2S)-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(7-methoxy-1,3-benzodioxol-5-yl)-2-phenylethyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(6-chloro-1,3-benzodioxol-5-yl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-3-phenylpropyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-3-phenylpropyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-bis(difluoromethoxy)-phenyl]-3-phenylpropyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-[4-(difluoromethoxy)-3-methoxyphenyl]-3-phenylpropyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(3-methoxyphenyl)-3-phenylpropyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[2-hydroxy-5-[2-hydroxy-3-[[1-(4-methoxyphenyl)-3-phenylpropyl]amino]propyl]phenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-3-[2-(trifluoromethyl)phenyl]propyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*))-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-3-[3-(trifluoromethyl)phenyl]propyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-3-[4-(trifluoromethyl)phenyl]propyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[3-(2-chlorophenyl)-1-(3,4-dimethoxyphenyl)propyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[3-(4-chlorophenyl)-1-(3,4-dimethoxyphenyl)propyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-4-phenylbutyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[bis[4-(difluoromethoxy)phenyl]-methyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-propanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-2-phenylethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-butanesulfonamide, trifluoroacetate (1:1); N-[2-hydroxy-5-[2-hydroxy-3-[[(4-methoxyphenyl)-methyl]amino]propyl]phenyl]methanesulfonamide, trifluoroacetate (1:1); (S)-N-[5-[3-[[(3,4-dimethoxyphenyl)methyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-3-butenyl]-amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (2S)-N-[5-[3-[[1-(3,4-dimethoxyphenyl)-3-methyl-3-butenyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]-methanesulfonamide, trifluoroacetate (1:1); [S- (R*,S*)]-N-[5-[3-[[3-cyclohexyl-1-(3,4-dimethoxyphenyl)propyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (S)-N-[2-hydroxy-5-[2-hydroxy-3-[(2-phenylethyl)-amino]propyl]phenyl]methanesulfonamide, trifluoroacetate (1:1); N-[5-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropyl]-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate (1:1); (S)-N-[2-hydroxy-5-[2-hydroxy-3-[[2-(4-phenoxyphenyl)ethyl]amino]propyl]phenyl]methanesulfonamide, trifluoroacetate (1:1); N-[4-[2-[[2-hydroxy-3-[4-hydroxy-3-[(methylsulfonyl)amino]phenyl]propyl]amino]ethyl]phenyl]-benzenesulfonamide, trifluoroacetate (1:1); (S)-N-[4-[2-[[2-hydroxy-3-[4-hydroxy-3-[(methylsulfonyl)amino]phenyl]propyl]amino]ethyl]phenyl]-4-(1-methylethyl)benzenesulfonamide, trifluoroacetate (1:1).
 10. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
 11. A method for treating diabetes, obesity, depression, achalasia or intestinal hypermotility disorders, which comprises administering to a mammalian species in need thereof a therapeutically effective amount of a compound as defined in claim
 1. 12. A pharmaceutical composition comprising a compound of claim 1 in combination with a beta₁ or beta₂ adrenergic blocker or stimulant and a pharmaceutically acceptable carrier.
 13. A method for treating diabetes, obesity, depression, achalasia or intestinal hypermotility disorders, which comprises-administering to a mammalian species in need thereof a therapeutically effective amount of a composition of claim
 12. 14. A compound of the formula

or a pharmaceutically acceptable salt thereof, or stereoisomers thereof, wherein R¹ is lower alkyl, aryl or arylalkyl; A is hydrogen or

B is hydrogen, alkyl, alkenyl, or

but when A is hydrogen, B may only be

R², R^(2′), R^(2″), R³, R³′ and R³ are independently hydrogen, hydroxy, alkoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, aryloxy, arylalkoxy, hydroxyalkoxy, lower alkyl, trifluoromethyl, halogen, cyano, alkylthio, alkylsulfinyl, alkylsulfonyl, -(CH₂)_(n)NR⁴COR⁵, -CONR⁴R^(4′), -CO₂R⁵, -NR⁴SO₂R¹, -NR⁴R^(4′), -OCH₂CH₂NR⁴R^(4′), -OCH₂CONR⁴R^(4′), -OCH₂CO₂R⁴, -PO₃R⁴R^(4′) or aryl; or R² and R^(2′) or R³ and R^(3′) may together form a carbocycle or heterocycle; m is 0−3; n=0−3; R⁴ and R^(4′) are independently hydrogen or lower alkyl; and R⁵ is lower alkyl.
 15. The compound as defined in claim 14 wherein R¹ is alkyl, m is 1, A is

and B is


16. A compound of the formula

wherein R¹ is lower alkyl, aryl or arylalkyl. 